Regeneration: Acute degeneration of rat pancreas acinar cells to less than 10 percent of normal was produced by protein-deficient diet and I.P. ethionine injection for 10 days. During the next 18 days (stock diet, discontinuance of ethionine) regeneration and full restitution occurred. This is the model for regeneration in current studies. Sufficient synchrony of cellular regenerative response existed during 5 days post-etionine to produce a wave of DNA synthesis peaking at the 4th day and mitoses at the 5th day. Objectives of the study have been to correlate LM and EM changes with corresponding biochemical changes during regeneration. Differentiation: In vitro organ culture of pancreas embryonic rudiments was instituted. A fully chemically defined medium was devised which supported parallel in vitro morphologic and enzymatic differentiation to that found in vivo. Reduction of methionine below a critical value was found to dissociate growth (low Met) from differentiation (high met.). Prolonged growth (to 10 weeks, protein increment 1000 fold) was feasible by periodic subdivision of the pancreatic tissue. This derived tissue maintained normal organ and cellular architecture and enzymatic components of fully differentiated tissue. The dissociation of growth and differentiation, feasibility of prolonged culture and demonstrated susceptibility of tissue to transformation by carcinogens makes this a model in vitro system. Efforts will be made to produce a post-ethionine regeneration in vitro with or without serum, embryonic extract or tissue.